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Turnover of receptor tyrosine kinases regulated by membrane trafficking

Research Project

Project/Area Number 26830080
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Tumor biology
Research InstitutionFukushima Medical University

Principal Investigator

uemura takefumi  福島県立医科大学, 医学部, 講師 (80548925)

Co-Investigator(Renkei-kenkyūsha) WAGURI SATOSHI  福島県立医科大学, 医学部, 教授 (30244908)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsゴルジ体 / エンドソーム / 受容体型チロシンキナーゼ / 小胞輸送 / タンパク寿命調節 / ノックダウン / 細胞増殖 / 癌 / 上皮成長因子受容体 / 細胞膜 / クラスリンアダプター / 細胞膜受容体 / 細胞内小胞輸送
Outline of Final Research Achievements

GGAs (GGA1,2,3) and AP-1 are membrane trafficking associated molecules and they function as clathrin adaptors. Their functions have been investigated in terms of quality control of protein using cell lines. Depletion of GGA2 or AP-1 complex decreased EGFR expression at protein level, reflecting enhanced lysosomal degradation of EGFR. This result suggests that GGA2 and AP-1 complex are involved in protein transport of transmembrane protein at the post-Golgi compartments to regulate the turnover. Also, this raises a possibility that the malfunction of GGAs and AP-1 could influence pathologies such as neurodegenerative diseases or cancer.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (15 results)

All 2017 2016 2015 2014

All Journal Article (9 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 9 results,  Open Access: 7 results,  Acknowledgement Compliant: 3 results) Presentation (6 results)

  • [Journal Article] Biallelic Variants in UBA5 Link Dysfunctional UFM1 Ubiquitin-like Modifier Pathway to Severe Infantile-Onset Encephalopathy.2016

    • Author(s)
      Muona M, Ishimura R, Laari A,...... , Komatsu M.
    • Journal Title

      Am J Hum Genet.

      Volume: 99 Issue: 3 Pages: 683-94

    • DOI

      10.1016/j.ajhg.2016.06.020

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] p62/Sqstm1 promotes malignancy of HCV-positive hepatocellular carcinoma through Nrf2-dependent metabolic reprogramming2016

    • Author(s)
      Saito T, Ichimura Y, Taguchi K, Suzuki T, Mizushima T, Takagi K, Hirose Y, Nagahashi M, Iso T, Fukutomi T, Ohishi M, Endo K, Uemura T, Nishito Y, Okuda S, Obata M, Kouno T, Imamura R, Tada Y, Obata R, Yasuda D, Takahashi K, Fujimura T, Pi J, Lee MS, Ueno T, Ohe T, Mashino T, Wakai T, Kojima H, Okabe T, Nagano T et al.
    • Journal Title

      Nature Commun

      Volume: 7 Issue: 1 Pages: 12030-12030

    • DOI

      10.1038/ncomms12030

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Activation of STING requires palmitoylation at the Golgi.2016

    • Author(s)
      Mukai K, Konno H, Akiba T, Uemura T, Waguri S, Kobayashi T, Barber GN, Arai H, Taguchi T.
    • Journal Title

      Nat Commun.

      Volume: 7 Issue: 1 Pages: 11932-11932

    • DOI

      10.1038/ncomms11932

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Differing susceptibility to autophagic degradation activity of two LC3-binding proteins: SQSTM1/p62 and TBC1D25/OATL1.2016

    • Author(s)
      Hirano, S., Uemura, T., Annoh, H., Fujita, N., Waguri, S., Itoh, T. and Fukuda, M.
    • Journal Title

      Autophagy

      Volume: 12 Issue: 2 Pages: 312-326

    • DOI

      10.1080/15548627.2015.1124223

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Sqstm1-GFP knock-in mice reveal dynamic actions of Sqstm1 during autophagy and under stress conditions in living cells.2015

    • Author(s)
      Atsushi Eino, Shun Kageyama, Takefumi Uemura, Hiromichi Annoh, Tetsuya Saito, Ichiei Narita, Satoshi Waguri, Masaaki Komatsu.
    • Journal Title

      Journal of Cell Science

      Volume: 128 Pages: 4453-4461

    • DOI

      10.1242/jcs.180174

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A cluster of thin tubular structures mediates transformation of the endoplasmic reticulum to autophagic isolation membrane2014

    • Author(s)
      Uemura T, Yamamoto M, Kametaka A, Sou YS, Yabashi A, Yamada A, Annoh H, Kametaka S, Komatsu M, Waguri S
    • Journal Title

      Molecular and Cellular Biology

      Volume: 34 Issue: 9 Pages: 1695-1706

    • DOI

      10.1128/mcb.01327-13

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Proteasome dysfunction activates autophagy and the Keap1-Nrf2 pathway2014

    • Author(s)
      Kageyama S, Sou YS, Uemura T, Kametaka S, Saito T, Ishimura R, Kouno T, Bedford L, Mayer RJ, Lee MS, Yamamoto M, Waguri S, Tanaka K, and Komatsu M.
    • Journal Title

      J Biol Chem

      Volume: 289 Issue: 36 Pages: 24944-24955

    • DOI

      10.1074/jbc.m114.580357

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 哺乳類オートファジー関連オルガネラの電子顕微鏡観察.2014

    • Author(s)
      和栗聡、植村武文、山本雅哉、矢橋あつ子
    • Journal Title

      顕微鏡

      Volume: 49 Pages: 118-123

    • NAID

      130007701709

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] オートファジー隔離膜近傍細管集合体の観察に用いるアルデヒド-オスミウム混合固定液の至適温度について2014

    • Author(s)
      矢橋あつ子, 植村武文, 和栗聡
    • Journal Title

      医学生物学電子顕微鏡技術学会誌

      Volume: 28 Pages: 9-11

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] ゴルジ‐エンドソーム局在型クラスリンアダプターGGA2は上皮成長因子受容体(EGFR)の安定化を介して腫瘍増殖を促進する2017

    • Author(s)
      植村 武文、和栗 聡
    • Organizer
      第122回日本解剖学会総会全国学術集会
    • Place of Presentation
      長崎市
    • Year and Date
      2017-03-28
    • Related Report
      2016 Annual Research Report
  • [Presentation] Sqstm1-GFP knock-in mice reveal dynamic action of Sqstm1 / p62 during autophagy and stress-conditions in living cells2016

    • Author(s)
      Atushi Eino, Shun kageyama, Takefumi Uemura, Hiromichi Annoh, Tetsuya Saito, Ichiei Narita, ○ Satoshi Waguri, Masaaki Komatsu
    • Organizer
      第121回日本解剖学会総会全国学術集会
    • Place of Presentation
      福島
    • Year and Date
      2016-03-28
    • Related Report
      2015 Research-status Report
  • [Presentation] 上皮成長因子受容体の分解と細胞増殖におけるGGA分子の機能2015

    • Author(s)
      植村武文、和栗聡
    • Organizer
      第74回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2015-10-06
    • Related Report
      2015 Research-status Report
  • [Presentation] オートファジー隔離膜の形成過程に関与する新規細管集合体2015

    • Author(s)
      植村武文、山本雅哉、安納弘道、小松雅明、和栗聡
    • Organizer
      第56回日本組織細胞化学会総会・学術集会
    • Place of Presentation
      枚方
    • Year and Date
      2015-10-03
    • Related Report
      2015 Research-status Report
  • [Presentation] ラット顔面神経切断縫合モデルにおけるクラスリン小胞輸送関連タンパク質の動態変化2015

    • Author(s)
      阪場貴夫、植村武文、和栗聡
    • Organizer
      日本解剖学会 第61回東北・北海道連合支部学術集会
    • Place of Presentation
      盛岡
    • Year and Date
      2015-08-29
    • Related Report
      2015 Research-status Report
  • [Presentation] 上皮成長因子受容体の恒常的分解と細胞増殖に関与するGGA分子の解析2014

    • Author(s)
      植村武文,和栗聡
    • Organizer
      日本解剖学会 第60回東北・北海道連合支部学術集会
    • Place of Presentation
      福島市
    • Year and Date
      2014-09-06 – 2014-09-07
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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